Tapentadol is both μ-opioid receptor agonist and norephinephrine (NE) reuptake inhibitor. Chemically, tapentadol is 3-(3-dimethylamino-1-ethyl-2-methyl-propyl) phenol. US RE39,593 discloses tapentadol as an analgesic composition and can be administered orally.
Conventional compositions (i.e. immediate release compositions) for oral administration of tapentadol lead to rapid release of the active ingredient in the gastrointestinal tract resulting in quick onset of action, but at the same time, a subsequent rapid reduction in the action is observed due to short half life (4 hrs) of tapentadol. The immediate release tablets comprising tapentadol marketed by Ortho McNeil Janssen under the brand name of Nucynta® in various strengths i.e. 50 mg, 75 mg, 100 mg is thus required to be administered 4-6 times a day (i.e. at every 4-6 hours), to ensure an adequately high concentration of the active ingredient in vivo for perceptible pain relief. If adequate pain relief is not attained with the first dose, the second dose may be administered as soon as one hour after the first dose. The maximum recommended daily dose is 700 mg on the first day and 600 mg on subsequent days. Combinations of tapentadol with other active ingredients such as analgesics have also been prepared.
US 2009/0099138 by Kalus et al., discloses a combination of tapentadol and one or more non-steroidal anti-inflammatory drugs (NSAIDs).
WO 2009067703 by Ramesh Sesha discloses pharmaceutical compositions comprising slow release tapentadol hydrochloride in combination with a second analgesic.
US 2005/0058706 by Johannes Bartholomaeus et al., discloses a slow-release pharmaceutical composition, containing tapentadol or a pharmaceutically acceptable salt thereof in a matrix wherein a peak serum level of the active ingredient is obtained in vivo within 2 to 10 hrs after administration of the composition. It also discloses simulation studies with repeated administration of the pharmaceutical composition at 12 hourly intervals, which showed that, serum levels are achieved and do not fall below 20 ng/ml, so good analgesic efficacy is ensured by twice daily administration.
Frequent dosing easily leads to errors in administration as well undesirable variations in concentration in the serum which are detrimental to patient compliance and the therapeutic benefit, particularly when treating chronically painful conditions. Therefore, controlled release compositions are desirable that maintains the therapeutic serum concentration of tapentadol for an extended period of time upon administration.
A controlled release pharmaceutical composition have now been developed comprising tapentadol for once-daily administration which ensures better patient compliance, wherein preferably the mean Tmax of tapentadol is reached after 10 hours of administration of the composition.